ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation.
Nat Cell Biol
; 23(6): 595-607, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-34108663
ABSTRACT
Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4CSA ubiquitin ligase. How CRL4CSA is specifically directed towards K1268 is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to K1268, revealing ELOF1 as a specificity factor that binds and positions CRL4CSA for optimal RNAPII ubiquitylation. Drug-genetic interaction screening also revealed a CSB-independent pathway in which ELOF1 prevents R-loops in active genes and protects cells against DNA replication stress. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between transcriptional stress responses and DNA replication.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Daño del ADN
/
ARN Polimerasa II
/
Factor 1 de Elongación Peptídica
/
Ubiquitina-Proteína Ligasas
/
Reparación del ADN
/
Ubiquitinación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Países Bajos